The broad objectives of this Program are to establish improved cytological criteria for evaluation of the clinical status, biological behavior, and response to therapy of human leukemia. In our laboratory a series of chromosomal alterations has been found to occur in repetitive fashion in patients with acute leukemia, suggesting that specific areas of the genome may play a role in leukemogenesis or in the evolution of the leukemic process. Sequential chromosomal studies indicate that in most patients a good remission is marked by early disappearance of abnormal clones, and that reappearance of these same chromosome alterations precedes relapse. The repetitive abnormal cytogenetic profiles associated with human acute leukemia will be fully analyzed and catalogued, and their potential use in the clinical evaluation investigated. In addition, our electron microscopic studies have demonstrated specific alterations of the nucleus of leukemic cells only in patients who have aneuploid clones. Similar nuclear alterations have also been found in cells exhibiting inhibition of DNA synthesis. This Program aims to investigate in more detail the association between ultrastructural and chromosomal alterations. This information will be utilized to determine: (1) if a defective DNA synthesis mechanism exists in aneuploid leukemias and (2) if this inherent defect can be exploited for more rational planning of chemotherapy. In addition this proposal intends to carry on a more in depth investigation of the cytogenetic abnormalities associated with myeloproliferative disorders and preleukemia to determine: (1) clinical significace (2) feasibility of using chromosomal markers for monitoring of therapy.